The placenta transports all of the building blocks required for fetal development. In particular, the placenta selectively transfers vital long chain polyunsaturated fatty acids (LCPUFA) to support the developing human brain and cardiovascular system. Adequate abundance of these specific fatty acids is crucial for normal development. Fetal deficiencies of LCPUFA are associated with compromised cardiovascular health, lower Intelligence Quotients (IQ), and behavioral and cognitive disorders that persist for life. Since the fetus has a negligible capacity to make LCPUFA, the main source is from the maternal circulation; a fetal deficiency of LCPUFA can arise from inadequate maternal levels or dysfunctional placental transport. In gestational diabetes, the mother's blood content of LCPUFA is normal but the placenta transfers significantly less LCPUFA, leading to subnormal levels in the fetus. The consequences of this are significant and these offspring display cognitive impairments and symptoms in accordance with LCPUFA deficiency. The mechanisms that underlie the dysregulation of LCPUFA transport in these placentas are poorly understood, especially in light of the fact that lipid transport even in normal pregnancies has been understudied. The goal of this project is to determine how the human placenta transports LCPUFA, first as it occurs in normal pregnancy and then to apply the knowledge gleaned to explain how this process is dysfunctional in mothers who have gestational diabetes. The process of LCPUFA transport has remained elusive because a method to track LCPUFA in real-time in the human placental tissue has not previously existed. This project proposes to live-track fluorescently tagged LCPUFA in human term placenta explants using state-of-the-art microscopy to identify the cellular mechanisms that underlie maternal-fetal LCPUFA transfer. It will first examine this process in placentas from normal, uncomplicated pregnancies. It will additionally examine how LCPUFA handling differs in placentas from mothers who are diagnosed with gestational diabetes. This study can lead to further investigations of potential biomarkers to evaluate dysfunctional placental LCPUFA transfer in vivo and may also help identify targets for strategizing molecular or nutritional interventions to support normal placenta LCPUFA transfer in pregnancies complicated by metabolic disease.